Cao Jicong, Perez-Pinera Pablo, Lowenhaupt Ky, Wu Ming-Ru, Purcell Oliver, de la Fuente-Nunez Cesar, Lu Timothy K
Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Nat Commun. 2018 Jan 8;9(1):77. doi: 10.1038/s41467-017-02587-w.
Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.
通过简化制造流程的技术可以解决当前按需药物制造的局限性。将两种或更多种药物的生产合并为一批，不仅对研究、临床研究和紧急治疗有用，而且在需要联合治疗或资源稀缺的情况下也有效。在此，我们提出了通过多重菌株开发、细胞培养、分离和纯化在单批中同时从酵母生产多种生物制品的策略。我们展示了三种生物制品联合生产策略的概念验证：（i）多种生物制品的诱导表达以及对共同生产的生物药物之间比例的控制；（ii）整合生物加工；以及（iii）两种单克隆抗体混合物的共表达和共纯化。然后，我们使用这些基本策略来生产药物混合物以及分离药物。这些策略为按需、灵活、低成本和分散式生物制造应用提供了各种各样的选择，而无需专门设备。
